The luteinizing hormone releasing hormone (LRH) is well recognized to be one of the six or seven or more neurohormones of the hypothalamus of mammalian species, including man. The hypothalamus is a part of the forebrain Prosencephalon which, unlike the cerebellum and the cerebral hemispheres, has maintained, throughout its phylogenetic history, a relative constancy of arrangement. Basically, the hypothalamus is divisible into medial and lateral portions. The medial division joins the third ventricle. The lateral portion of the hypothalamus contains cells that are diffusely arranged among the fibers of what has long been called the medial forebrain bundle. An anatomic relationship which is a constant feature of the hypothalamus is its intimate association with the pituitary gland. The pituitary gland consists of the posterior and antierior lobes. Biochemical transport of the neurohormones of the hypothalamus to the anterior lobe is provided by certain blood vessels in a portal system which is a network of capillaries. The blood of these capillaries passes down the pituitary stalk and becomes distributed through another system of capillaries in the anterior lobe and one of the neurohormones thus transported is LRH.
In addition to LRH, there is a follicle stimulating hormone releasing hormone (FRH) and a prolactin releasing hormone (PRH). It is generally considered that there is one hypothalamic releasing hormone for each of the pituitary hormones of the anterior lobe, but this concept has not yet been proven. However, it has been established that there is a hypothalamic neurohormone which releases the luteinizing hormone of the anterior pituitary; that is, LRH. It appears that LRH also releases FSH, at least to some extent.
Presently, LRH is extracted from animal hypothalamic tissue obtained from many thousands of animals at slaughter houses with great difficulty since the size of the hypothalamic tissue from a full grown pig is only about 150 mg. The enormous task involved in obtaining pure LRH from animal tissue is exemplified by the fact that less than 0.5 mg. of purified, but not completely pure, LRH was obtained from the combined tissue of about 80,000 sheep. (Guillemin, International Journal of Fertility, Vol. 12, No. 4 pp. 359 (1967).) Guillemin stated that "the difficulties involved in the isolation of LRH are such, however, that we must consider as absolutely out of the question the use of hypothalamic hormones of natural sources for our clinical studies." It can be seen, therefore, that scientifically, LRH has been obtained in only very minute amounts and incompletely freed of impurities. Thousands, and sometimes hundreds of thousands, or hypothalamic fragments from as many animals are required to obtain minute quantities of the natural hormone and even then it is of doubtful total purity.
Working initially with 165,000 pig hypothalami, Schally, et al. (Biochem. Biophys. Res. Commun., 43, (2), 393 (1971) ), ultimately obtained 830.mu. g of material which still was not completely pure, but which released both LH and FSH. This very limited quantity of material represented purification of over two million-fold.
It is clearly evident that the naturally occurring LRH derived from slaughter house tissue can hardly be obtained in sufficient quantity and purity to permit even the most exploratory diagnostic studies in medicine, and that obtaining LRH from this tissue for widespread practical use in medicine is impossible.